Monday, May 31, 2010

On Saturday we went to the Chichester Festival Theater to see the new "Yes Prime Minister". I had not been to the Chichester Theater since 1967 when I saw Alec Guinness in "Merchant of Venice" (he wasn't very good, in fact I also saw him on stage as Samuel Pepys and he wasn’t good in that either. He was a better film actor. Film demands stillness; the stage motion).

"Yes Prime Minister" is one of my favorite TV comedy series and I wondered how it would play on stage. There are several difficulties to overcome. First there is the fact that Nigel Hawthorne and Paul Eddington made the parts of Sir Humphrey and Hacker so much their own. Then there is the difficulty of expanding the shows into a full two hours. Finally, there is the problem of how the gentle comedy will play with today's coarser politics, especially after programs like "The Thick of It".

The theater is still magnificent and has wonderful acoustics. I saw fellow CLL specialist, Daniel Catovsky in the audience, but he was too far away to speak to him.

I'm afraid that the two principals, Henry Goodman and David Haig didn't reach the required standards. They are well-known character actors who are seldom out of work. Both have appeared with Hugh Grant in either "Notting Hill" or "Four Weddings", but the parts are so identified with the late Hawthorne and Eddington, that they are stuck between aping their predecessors and trying to create new characters.

Mind you, Jonathan Slinger as Bernard Wooley (previously Derek Faulds who is still alive) was much worse. I think he played him as gay.

The plot really didn't last for two hours. As time went by it grew more and more implausible until they were reduced to implications that were both offensive and profane.

Afterwards we had time to kill so we wandered around Chichester, which obviously, from its name, derives from Roman times. It has a fine (though small) Norman cathedral, unusually with a separate bell tower. The spire has been added later, but there are some fine examples of modern art including a Piper frontal and a Chagal window. Chichester still has a feel of a small country town with interesting shops. It looks a nice place to retire to, being handily placed for the sea and the new South Downs National Park.

We had dinner at the Earl of March, a gastropub some 5 miles north of Chichester. I had the sea bream which was very good.

Chichester is only an hour’s drive from Bournemouth, so we will probably go again.

Sunday, May 23, 2010

Last week we wrote about leaders; this week we write about followers. In the military they talk about insubordination and mutiny as amongst the most heinous crimes. People like Kim Philby and Burgess and MacLean, spies who leaked secrets to the Soviets, are thought of as the most disgusting of traitors, but soldiers or sailors who refuse to obey legitimate orders, often out of cowardice, are just as effective agents of the enemy.

Sir Francis Drake, when he was singeing the King's beard at Cadiz in 1587, had a subordinate, Sir William Borough, commander of the frigate, the Red Lion, who refused Drake's order to sail into Cadiz Harbour, thus endangering the whole expedition. Even though Borough was a Vice-Admiral, Drake had him clapped in irons and charged with Mutiny. These were in the days when the rules of discipline in the Royal Navy were less well developed than now and it was perhaps just, that the trial collapsed. But the point is well made that without willing followers as well as good leaders, and enterprise is doomed.

Young men, in the same way be submissive to those who are older. All of you, clothe yourselves with humility toward one another, because, "God opposes the proud but gives grace to the humble." Humble yourselves, therefore, under God's mighty hand, that he may lift you up in due time. Cast all your anxiety on him because he cares for you. Be self-controlled and alert. Your enemy the devil prowls around like a roaring lion looking for someone to devour. Resist him, standing firm in the faith, because you know that your brothers throughout the world are undergoing the same kind of sufferings. 1 Peter 5:5-9.

'Those who are older' is a mistranslation. Every other version refers to 'elders', those holding that office in the church. But why are young men singled out?

For one thing, young men are very truculent; they think they know it all. I know; I have been a young man. It may be the soaring testosterone levels, but young men won't be told. When I was young, I called older people old-fashioned. I espoused everything modern. I was cheeky to the elderly - I thought that they had had their day and should step out of the way. The times they are a-changin' was my theme song.

Come mothers and fathersThroughout the landAnd don't criticizeWhat you can't understandYour sons and your daughtersAre beyond your commandYour old road isRapidly agin'Please get out of the new oneIf you can't lend your handFor the times they are a-changin'.

Were you the same?

But there is another, equally compelling reason to address young men. The young men of today will be the leaders of tomorrow and the best leaders must first learn what it is to be a follower. The Biblical pattern is exemplary. King David served his apprenticeship as a shepherd, Elisha, ploughing with oxen, and Amos tending his vines. Even Jesus was an apprentice builder! When we were medical students, before we were allowed on the wards, we had to spend two weeks acting as nursing auxiliaries. Our chief task was emptying bed-pans.

But it is not only young men who must learn to be humble, Peter continues, "All of you, clothe yourselves in humility."

I wonder, do you find humility difficult? When people really appreciate how good you are, do you find it difficult to turn down praise? I mean, isn't it false modesty to pretend you don't deserve it?

You see how easy it is to get into that mind set?

Pride is so surreptitious. It creeps up on us. Which of us isn’t proud of our upbringing, or our school, or our home, or our family, or our children’s attainments or our country? Yet what we have, we have as a gift from God.

We have to both put on humility to each other and to God. To be humble before God, but not before each other is hypocrisy

Being humble isn't thinking yourself worthless; you are valued by God. Jesus was our object lesson in humility; but he knew he wasn't worthless. It is about knowing that you are valuable, but disdaining the glory that goes with it and holding back.

Nor is it refusing to use your gifts - that's pride. You are being proud because you fear humiliation. Being humble means being willing to risk humiliation. Note that Peter tells us to 'clothe ourselves with humility'. Don't be put off by the accusation that you are 'putting it on'. Of course you are. We are naturally proud; humility doesn't come easy.

When I learned to play golf the grip on the club seemed unnatural to me. I was used to playing cricket and the aim in cricket is to hit the ball all along the ground. To hit the ball in the air you put your weight on the back foot. Weight on the back foot and a cricket grip in golf will mean you will 'top' the ball, if you don't play a complete 'air' shot. To get good at golf you have to practice. You 'put on' something that is unnatural and keep at it. So it is with humility. It's not natural; you need training. With practice it becomes second nature, but our first nature is corrupt.

Peter instructs us to "humble ourselves under God's mighty hand." Humbling ourselves before God means realizing that we depend on him for everything; it means not being self-reliant, but being God-sustained. It means taking the lower seat and waiting for the invitation to "Come up higher". We can only achieve humility before the Lord with the Lord's help, so prayer is vital. Rest assured the invitation will come. Does not Peter tell us that he will "lift you up in due time". It is a hard task to rely on God alone and not to trust to our own strength.

A story is told of a man who falls over a cliff, but clings on to a branch growing out of the cliff face. He cries for help, "Is anybody up there?" No reply. He's getting desperate. Again, he cries, "Is anybody up there?" A deep voice comes from the clouds, "I am here my son. Just let go of the branch and I will catch you."

The man grips the branch tightly as he ponders his predicament. Then he shouts again, "Is anybody else up there?"

As I said before, we are not very good at the humility thing. There needs to be some repentance. It's not that we are not forgiven, but we sure haven't changed yet.

There is an important reason for us not to be proud. "God opposes the proud". I suspect most of us would prefer not to be opposed by God. On the other hand he "gives grace to the humble". And it is only through his grace that humility is possible.

But we must not only be humble, we must also be disciplined. We must be "self-controlled and alert", for while we do have God on our side, we also have an enemy. The Devil prowls about like a roaring lion.

Have you seen those films of the African Savannah? Great herds of antelope and a pride of lions; who is it that the lions attack? It is those who are the weakest and those who get separated from the herd. How important it is to be part of the local church, with brothers and sisters in Christ to protect us. This is not a game; it is deadly earnest. In order to pray meaningfully we must be disciplined. It is not a matter of reciting a set prayer – saying your prayers. Our prayers should be an informed conversation with God. It helps to have a prayer partner. It helps to study the Bible. It helps to be integrated into church life.

Currently, our brothers and sisters in the Christian church in Morocco are being expelled from home and hearth by a fundamentalist Muslim Chief of Police. Peter tells us to stand firm in the faith because you know that your brothers throughout the world are undergoing the same kind of sufferings.

There is a battle waging. There will be casualties. The foe we face is a defeated foe, but he is still capable of inflicting wounds. He lashes out in frustration and anger, but even should we die we cannot perish. Just as our Lord Jesus was not defeated by death, no more shall we be. We are more than conquerors, through him who loved us.

So put on the whole armor of God; the belt of truth, the breastplate of righteousness, our feet shod with the gospel of peace, the shield of faith, the helmet of salvation and the sword of the Spirit.Have you heard the phrase, ‘The Birkenhead Drill’? It is not some implement from the industrial revolution, but a standard of discipline.

HM Troopship Birkenhead was one of the first iron-hulled ships built for the Royal Navy. On 26 February 1852, while transporting troops primarily of the 73rd Regiment of Foot to Algoa Bay, she was wrecked at Danger Point near Gansbaai on the outskirts of Cape Town, South Africa. There were not enough serviceable lifeboats for all the passengers, and the soldiers famously stood to attention, thereby allowing the women and children to board the boats safely. Only 193 of the 643 people onboard survived, and the soldiers' chivalry gave rise to the "women and children first" protocol when abandoning ship, while the "Birkenhead drill" of Rudyard Kipling's poem came to describe courage in face of hopeless circumstances.

To take your chance in the thick of a rush, with firing all about,Is nothing so bad when you've cover to 'and, an' leave an' likin' to shout;But to stand an' be still to the Birken'ead drill is a damn tough bullet to chew,An' they done it, the Jollies -- 'Er Majesty's Jollies -- soldier an' sailor too!Their work was done when it 'adn't begun; they was younger nor me an' you;Their choice it was plain between drownin' in 'eaps an' bein' mopped by the screw,So they stood an' was still to the Birken'ead drill, soldier an' sailor too.

It requires courage to face the Devil, but we do not have a hopeless cause.

Yesterday I received a message from the Facebook team to let me know that someone had left a message telling me that "This is really hilarious". Foolishly I tried to open it. Of course it turned out to be a virus of sorts. I don't think it does any harm except to sent a similar message to all my Facebook friends. It gets through McAfee. If you have had a similar message from me and have not yet opened it. Please don't.

Saturday, May 22, 2010

The first thing is don't panic. Three quarters of cases are diagnosed because you had a blood test for something else. When it is first diagnosed you have probably had it for years, so the day of diagnosis is not a special day in the history of your disease. It may be a special day in your life, but your disease isn't interested in that. It is plodding its weary way along a long path and it just so happens that it has been noticed for the first time.

You sometimes hear people say, "I was lucky; the doctors caught it in time." For CLL, there is absolutely no evidence that catching it early makes any difference to the outcome. Almost certainly the first type of management you will be offered is watch and wait and about a quarter of patients will never need treatment.

In the old days doctors never used to tell a patient that they had CLL so as not to frighten them and there was some merit in this. We now call many cases of what was then known as CLL by a different name. They are now called monoclonal B cell lymphocytosis (MBL) which is believed to turn into CLL at the rate of 1% a year. Since the average age of diagnosis is 70, in most patients this is never going to happen. There are still patients walking around with the diagnosis of 'leukemia' attached to them worrying about their future when they shouldn't be.

As an aside I should say that the same is probably true for certain types of cancer as well. Prostate cancer and breast cancer are examples of this - especially when the diagnosis has been made by a screening test.

We need to explore the reasoning behind watch and wait. Some twenty years ago there were a lot of trials involving more than 2000 people who were randomized to treatment at the time of diagnosis or treatment when the disease progressed. There was absolutely no difference in survival. Indeed there was a suggestion at 6 years follow up that those who had treatment did slightly worse.

I need to qualify this reasoning. At the time of the trials, treatment was not very good - nobody got cured however early they were treated. Also at that time we had no way of picking which patients would progress and which would not. So some patients who would never need treatment were treated unnecessarily.

Because of this some people think it is necessary to repeat these trials, only this time confining treatment to those who are just about guaranteed to need treatment eventually and using agents that are much more effective than they were 20 years ago. These trials are taking place in Germany, the USA and the UK, but because the outcome measure is overall survival we will not be getting an answer anytime soon.

So how does a doctor work out who needs treatment? Some patients clearly need treatment pretty soon. These are picked out by either symptoms or clinical stage. Some patients are definitely ill when they are first seen. Those with fever that isn't caused by an infection, or severe fatigue that really stops them doing anything, or weight loss - more than 10% over the past 6 months (that wasn't being aimed at by a diet and exercise program) or such severe sweats at night that they have to change nightclothes or even bedclothes. Such symptoms are usually the result of a large volume of disease - which may not be apparent on clinical examination, because it is located at the back of the tummy behind all the normal tummy organs (so called retroperitoneal disease).

It is also generally agreed that patients with Rai stage 3 or 4 or those with Binet stage C disease need treatment. Kanti Rai from Long Island and Jacque-Louis Binet from Paris are very senior CLL specialists who gave their names to staging systems that are used in America and Europe respectively. Rai stage 3 or 4 and Binet stage C are signs that the bone marrow has started to fail. Rai stage 3 means the hemoglobin (Hb) is less than 11 g/dL and Binet stage C means that the Hb is less than 10 g/dL. I have no idea why the two experts chose different levels as a trigger nor why it is the same for men and women. An Hb of 10 for a man means that he has lost 3.5 g while an Hb of 11 for a woman means she has lost only 0.5 g. Crazy isn’t it?

In my own practice I tend to take an Hb of 10 as a trigger for treatment, though I am quite willing to start if I see a consistent downward trend. Incidentally you will see that I am using Hb as an abbreviation for hemoglobin rather than Hg which many patients tend to use. The reason for this is that Hg has already been taken; it is the chemical symbol for mercury, which we use in medicine when measuring blood pressure. Aim for 120/80 mm of Hg. It is also important to be sure that the low Hb is caused by marrow failure. It would be silly and fruitless to use chemotherapy to treat simple iron deficiency. This is especially important when the anemia is cause by autoimmune hemolysis (which occurs in 15% of patients with CLL). The treatment for autoimmunity in CLL is usually steroids, and only if it can’t be controlled by steroids is it right to treat the CLL.

The trigger level for a low platelet count to start treatment is 100,000 per cu mm for both European and American staging systems. Again, this is a bit arbitrary. Sometimes, the platelet count will hover around 100,000 for months. It doesn’t necessarily mean that treatment starts when it touches 99,000 for a few hours. We are more concerned by the rate of fall. We might start treatment at 120,000 if the fall is very rapid. We have to worry about autoimmunity with platelets also and about a condition called hypersplenism where a large spleen acts as a reservoir for platelets so that they are rather low in the blood. Neither is an indication for treatment, but there is no easy test for either of them. Most times the doctor has to make a judgment call.

Other reasons for beginning treatment relate to the size of the spleen or enlarged lymph nodes. Here again we run into a problem because the staging systems were designed to be operated without using CT scans. You are Rai stage 2 because your spleen can be felt, not because a CT image says it is enlarged. The spleen is an organ whose job it is to get rid of dead and dying blood cells, but it also has important jobs to do in the immune system. It lives under the ribs on the left and as it enlarges it migrates towards your belly button. When you take a big breath you can feel it emerge from beneath the ribs. The pundits have decreed that treatment should begin when the spleen is enlarged 6 cm below the edge of the ribs (that’s 2 and a half inches for those not used to metric measurements). In real life that means that the spleen is about three times its normal size.

The same problem involves lymph nodes. The staging systems are about what you can feel, not what you can see on a CT scan. Doctors are expected to look in the neck, under the armpits and in the groin. Any node or group of nodes that is 10 cm (4 inches) in diameter is an indication for treatment.

What is not an indication for treatment is the height of the white count. For other types of leukemia high white counts are a worry because they can cause sludging in small blood vessels and lead to a stroke or blindness. This does not happen in CLL. Even if your white count is a million, it is not dangerous. However, rapid rises in white count may be an indication of rapid progression of your disease and rapidly progressive disease needs treating. If your white count doubles in six months then treat. If it increases by 50% in two months, then treat. There is a proviso here. It is not the rate of increase that matters but what it represents. It represents rapidly progressing disease. But if the white count goes up because of an infection or a vaccination or because you have had some steroids it doesn’t represent rapidly progressive disease and it isn’t an indication for treatment. Also, if it starts from a low base – less than 30,000 – then there is no correlation with disease progression and it should be ignored. Rapidly progressive disease can also be recognized if the spleen or lymph nodes enlarge over a short period of time, no matter what is happening to the white count.

So to summarize: 1] There is no point in treating CLL just because you have it. In most cases you can’t cure it. 2] If it is causing symptoms it ought to be treated for symptom relief. 3] If it is causing organ failure (usually the bone marrow)it ought to be treated to spare the failing organ. 4] If it is progressing rapidly it ought to be treated because it will kill you if it isn’t.

Thursday, May 20, 2010

One of the stranger films in my collection is the 50 year old 'Conspiracy of Hearts', a second world war drama set at the time when the Italians surrendered but the German Army briefly took over control in Italy before the Allies overcame them. It is set in a holding camp for Jewish children, still run by Italian soldiers, although following Nazi orders. The Italian major, played by Ronald Lewis, with a fine upper class English accent, turns a blind eye to the activities of a convent of nuns, led by Lilli Palmer, who are smuggling about 10 children a night out of the camp and away to the Partisans. Sylvia Sims (fresh from Ice Cold in Alex) is a willowy blonde novice and Yvonne Fletcher plays a German nun who thinks that it is not their place to break the law. Michael Goodliffe, one of those actors whose face you know but can't quite place (he was the second Hunter in 'Callan'), played the local priest. Look out also for Jenny Laird from 'Black Narcissus'.

Things get more complicated when the Germans take over the camp. Acually there were only two, Colonel Erich Horsten played by Albert Lieven (the German actor, on stage from 1928, who fled the Nazis during the war years, only to portray Nazi menacers in British films; he was the grandfather of England rugby player, Toby Flood) and Lt Schmidt (Peter Arne). The Colonel follows orders (even though he thinks they are crass) and the Lieutenant follows orders because he is a Nazi.

Of course, the nuns are caught and nice little moral dilemmas are set up.

Most of the actors are now dead. Lewis and Goodliffe committed suicide and Arne was murdered. Fletcher died young from Breast Cancer. Lilli Palmer was famously married to Rex Harrison. Only Sylvia Sims survives and is still working, though no longer slim and beautiful - quite the reverse on both counts.

The producer/director team of Betty Box and Ralph Thomas abandoned serious themes thereafter and concentrated on the 'Doctor' comedies and the early 'Carry on...' farces. Thomas directed Dirk Bogarde 9 times and James Robertson Justice 13 times.

One of the writers was Adrian Scott, a member of the Hollywood Ten.

The film was nominated for a Golden Globe as the film most likely to promote international relations (though not with the Germans, I think).

Tuesday, May 18, 2010

Yesterday the temperature in Bournemouth was hotter than anywhere else in Britain and today is warmer still. We have had a very cold Spring. The apple blossom was late and the camellias and magnolias are still blooming. The daffodils were also late and tulips are still in flower.

I was just in the garden and what was noticeable was the smell of lilac and Mexican Orange. Scents have returned and Spring has properly arrived.

Last week we had the decorators in, painting the back of the house and they followed the roofers who seem finally to have cured the leak in our bedroom ceiling. We have a couple of weeks with the house to ourselves before the decorators return to paint the front and sides and then in July most of the inside.

For the last couple of weeks I have been having colicky abdominal pains. Of course, I immediately thought I was relapsing, but things seem to have settled now, so I guess it was just nerves. I am due another CT scan on June 21st.

Alfred Hitchcock made 53 films and I have just updated my collection so that I now have 48 of them. Very probably the remaining 5 are not worth having, but if they are I am sure that I will only find them in rare collections that are quite expensive and mean duplicating those that I have. I remember having the same problem with Haydn symphonies when I was collecting them. My DVD collection currently stands at 1233 movies. I have pretty well all that I want, though I still have to convert some VHS films to the DVD format. Shall I then transfer to Blue-Ray? I don't think so.

Among the other things that I have been doing is writing a Christian version of "Love changes everything" Here it is:

Love, Love changes everything: Treasures truth and Scorns the lie; Love, Love changes everything: How you live and How you die.

Love Was born of sacrifice On a cross That bought my freedom.

Yes, Love, Love changes everything: Now I tremble At your Name. Nothing in the World will ever Be the same.

Monday, May 17, 2010

There are a lot of people who have been told that they have T-CLL. Many years ago this was a proper diagnosis. Indeed, it was taught that there were two types of CLL: B-CLL and T-CLL. This is no longer the case. What used to be called B-CLL is now just CLL (or CLL/SLL) and what was T-CLL is a number of different conditions.

T-PLL is the condition most commonly mixed up with CLL. It comprises about 2% of mature lymphoid leukemias. It occurs in the same age group and the cells in the peripheral blood film look similar though on average the cells are slightly larger than those of CLL, the cytoplasm tends to be bluer. Although in most cases a nucleolus is visible, in 25% of cases it is not. The characteristic feature is of surface blebs in the cytoplasm. Occasionally the nucleus is very irregular.

The immunophenotype shows positivity for CD2, CD3, CD5 and CD7. B-cell markers are negative. Most cases are CD4+, CD8-; but in 15% it is the other way round and in 25% they are doubly positive. TCL1 overexpression can be demonstrated by immunohistochemistry and the TCR genes are clonally rearranged. The commonest chromosomal abnormality is inversion 14 (q11;q32) which is seen in 80% of cases and in 10% there is a reciprocal translocation t(14;14)(q11;q32). These all involve the TCA@ and TCL1A and TCL1B loci. Often the karyotype is complex with abnormalities of chromosome 8, deletions at 12p13 and 11q23 and sometimes p53 abnormalities.

T-PLL is more aggressive than CLL. It presents with an enlarged liver and spleen as well as widespread lymph node enlargement. The skin is involved in 20% of cases. Anemia and thrombocytopenia are usual and the white count usually exceeds 100. Serum immunoglobulins and HTLV1 serology are normal.

The median survival is less than a year, although more chronic cases have been reported (I saw one patient who responded well to chlorambucil for more than two years). The best responses have been seen with Campath. A trial of PARP1 inhibitors has started. Stem cell transplant should be explored in patients who are young enough and who have a donor.

The other condition most commonly confused with CLL is large granular lymphocytic leukemia (LGL leukemia). This is a heterogeneous disorder characterized by a persistent increase in large granular lymphocytes (usually between 2 and 20) without an obvious cause. LGL leukemia comprises 2-3% of mature lymphoid leukemias. Most cases are CD3+, CD8+ and show a clonal rearrangement of the TCR alpha beta genes, but occasional cases express CD4 rather than CD8 and gamma delta genes rather than alpha beta. Loss of CD5 and CD7 is rather common. Expression of CD57 and CD16 is usual. However, not all cases are derived from T-cells - some seem to be derived from NK cells and some have evidence of a mixed origin.

NK cells have CD56, CD57 and CD16 on their surface and NK-associated MHC class 1 receptors CD94/NKG2 and KIR families. Expression of a single isoform of KIR receptor is accepted as evidence of NK monoclonality. It is sometimes difficult to distinguish between T and NK LGL leukemias.

There are no characteristic chromosomal abnormalities.

Non-malignant conditions may mimic LGL leukemia. Felty's syndrom (rheumatoid arthritis with splenomegaly and neutropenia) may be a separate disease or part of the clinical picture. LGLs are increased post splenectomy, post stem cell allograft and in autoimmune diseases.

Clinically, LGL leukemias are almost always indolent. Neutropenia and moderate splenomegaly may be seen and most cases do not require treatment. Treatments that have been tried with some success include splenectomy, cyclosporin A, cyclophosphamide, steroids, low dose methotrexate and pentostatin.

Sezary syndrome is sometimes mistaken for CLL. Although the circulating tumor cells are characteristic with 'cerebreform' nuclei, the nucleus may be contracted and quite small, so that it escapes detection. Sezary syndrome is a disseminated form of mycosis fungoides and therefore has its origin in the skin. One finds generalized erythroderma (red skin), enlarged lymph nodes and the characteristic cells in the blood.

Sezary syndrome accounts for only 5% of skin T-cell lymphomas, and since skin lymphomas are usually the province of dermatologists, they represent the only skin tumors that hematologists are likely to see.

The immunophenotype is CD2, CD3, CD5 and TCR beta positive. Most cases are CD4+ and expression of CD8 is very rare. They express the cutaneous lymphocyte antigen (CLA) and the skin-homing receptor CCR4.

The clinical features apart from those mentioned are are itching, hair loss, thickening of skin on the palms and soles, nail atrophy, and problems with the eyelids. It is an aggressive disease with only 5-10% surviving for 5 years. Treatment is experimental but may include fludarabine, pentostatin, steroids and immune therapies.

Sunday, May 16, 2010

In the UK we have just had a change of leadership. Gone is the unpopular Gordon Brown; our new Prime Minister is David Cameron. Cameron has never held office before and has been trying to redefine the Conservative Party, which had acquired the name of the Nasty Party following the introduction of the Poll tax under Margaret Thatcher.

The electorate were unable to give Cameron a proper mandate and saddled him with a companion in power, Nick Clegg. Although they come from different parties, Cameron and Clegg are surprisingly alike. Both are very rich, both were privately educated at expensive schools and at Oxford/Cambridge University, both are 43 years old and both have very glamorous wives. Cameron is related to British Royalty, Clegg to European Nobility. One has a blue tie and one a yellow tie, but they could be Bill and Ben, the flowerpot men.

Perhaps it is significant, but in our studies in 1 Peter we have come to an end of our suffering and begun a section on leaders.

To the elders among you, I appeal as a fellow elder, a witness of Christ's sufferings and one who also will share in the glory to be revealed: Be shepherds of God's flock that is under your care, serving as overseers—not because you must, but because you are willing, as God wants you to be; not greedy for money, but eager to serve; not lording it over those entrusted to you, but being examples to the flock. And when the Chief Shepherd appears, you will receive the crown of glory that will never fade away.

Somebody said that we get the leaders we deserve. I suppose that if you let other people impose leaders on you, you deserve all you get, though some have little choice about it. In churches you have the option to go somewhere else, but you seldom have that choice in a country. However, many churches give the members a say in who comes as a leader, and here Peter, gives us some guidelines as to what we should look for in a leader.

He writes, not as a Bishop or Archbishop, still less as a Pope, but as a fellow elder. There is no hierarchy in the Christian church. Peter was an apostle. We learn in Acts that he had special powers to confer the Holy Spirit (remember how Simon Magus coveted them). He had been a witness to the suffering Christ (admittedly he had fled from the crucifixion, but the whole ministry of Jesus had been one of suffering). If anyone had a right to lord it over the other ministers in the early church, it was Peter; but he calls them fellow elders. This doesn't mean that our leaders should be elderly, but they should be mature believers - not young in the faith. Many of the disciples were young men and Jesus himself was not elderly. John the Apostle certainly lived to a ripe old age, but he began his ministry while young. The great preacher CH Spurgeon was hardly more than an infant when he began his ministry, but he had a remarkable maturity.

Leaders are not to be dictators. One of the great tragedies of the Christian church has been its attempt to ape secular leaders. Church leaders should not dress up in expensive uniforms or issue edicts from thrones. I hate the expression "My Lord Bishop". They are not Lords. We have one Lord and Savior, and him Christ Jesus. But if they are not to be dictators, they are not to be nannies either. We have got into a rut in the UK of expecting everything to be served up for us on a plate. The NIV has interpolated the idea of a servant here. The word occurs twice in verse 2 'serving as overseers' and 'eager to serve', but it is nowhere in the Greek. The ESB renders verse 2 more accurately as shepherd the flock of God that is among you, exercising oversight, not under compulsion, but willingly, as God would have you; not for shameful gain, but eagerly;

Leaders are indeed servants, but servants of God, as we are all to be. If we are to follow Jesus, we must certainly be willing to humble ourselves and wash each others feet, but we must balance the injunction to carry each other's burdens (Galatians 6:2) with Paul's determination not to be a burden to anyone (2 Corinthians 11:9). Some congregations see their minister as their personal servant. Paul left instructions that where possible people should make arrangements to carry their own burdens so as to not let the church be burdened with them (1 Timothy 5:16). There are enough really needful people.

Secondly, leaders must be shepherds or pastors. Scripture gives us so many examples of the pastoral role. The 23rd Psalm talks of leading and guiding, protecting and comforting, providing life-giving spiritual food and refreshing spiritual water. The parable of the shepherd talks of seeking the lost and fetching back the fallen. John's Gospel tells us that the good shepherd lays down his life for the sheep.

We need a shepherd. One of the worst fates to behold us would be to be as sheep without a shepherd. We would wander and stray into danger; we would be unprotected and prey to all sorts of devilish dangers.

Jude warns us against false leaders who might slip in amongst us. He calls them shepherds who feed only themselves. Alas there are such leaders in the church today; clouds without rain, autumn trees without fruit, wild waves of the sea, wandering stars. These men are grumblers and fault-finders; they follow their own evil desires; they boast about themselves and flatter others for their own advantage.

We need shepherds who feed the flock with sermons that teach the Scripture and who tend the lambs and sheep - and here I include small group leaders who are aware of every problem and difficulty of their own small collection of believers.

Thirdly we need overseers. In the Greek it is Epi-scopos; it is sometimes translated bishops, but we must avoid what that word has come to mean. It is not a hierarchical office. Leaders must be men of vision; people who see the big picture. Those who recognise context, who see where things are going; men of strategy. They must be aware of what is happening in the Christian world. Assuredly new movements arise and will arise. Sometimes there is something we can learn; oftentimes they are flawed and lead into error. The Lord gives discernment as one of the gifts of the Spirit and we must covet that gift for our leaders. Our leaders must be readers. They must know what is going on out there as well as what is happening in here.

How should our leaders do their work? First, willingly. We don't need pressed men. We must welcome good leaders and treat them well so that their work does not become a come a chore. They must have sufficient time off to refresh themselves in the Word. They must have someone that they can talk to and thrash out their problems. What a pleasure it is when coming to work is a pleasure. Our leaders are human, not demigods. We must pray for them and encourage them.

Second, eagerly. Our leaders should be full of zeal. When God chose someone to take the word to the gentiles, he didn't chose someone with the experience of being with Jesus throughout his ministry, he didn't choose someone who had witnessed the crucifixion or someone who had seen all the miracles or even someone who had imbibed the whole of the teaching of Jesus. He chose someone who was a man of zeal; Saul of Tarsus; someone who up until then had been in the enemy's camp. Zeal is irreplaceable. Have you had the experience of listening to the sermons of someone who is just going through the motions? Boring isn't it? Enthusiasm alone can lead people astray, but correct teaching without enthusiasm sends people to sleep.

Thirdly, our leaders must be examples to the flock. We look to them to see the fruits of the Spirit acted out. Love, joy, peace, patience, kindness, goodness, faithfulness, gentleness and self-control. Or as Peter puts it in his second letter: For this very reason, make every effort to add to your faith goodness; and to goodness, knowledge; and to knowledge, self-control; and to self-control, perseverance; and to perseverance, godliness; and to godliness, brotherly kindness; and to brotherly kindness, love. For if you possess these qualities in increasing measure, they will keep you from being ineffective and unproductive.

Why is it that our leaders lead? Verse 4 tells us. Our real leader is the Lord Jesus Christ and one day he will return. And when he returns we will receive a crown of glory. That is not a crown that will tarnish or fall apart. It is not a party hat that you get from a Christmas cracker. It is the imperishable, "Well done, thou good and faithful servant."

Saturday, May 15, 2010

You find some funny things in the medical journals. In the Journal of Nutrition 2010; 140:1007-13, we read of a Japanese study which concluded that coffee drinking had a beneficial effect on morality in women. Funny, I thought, I'd heard of Tea ceremonies and Geisha girls. Then I realised. Replacing the 't' in morality is a life taking experience.

I'm not sure what to make of these.With the possible exception of II,which like all Roman numeralsis subject to misinterpretation,I see no cause for alarm.I admit to a preference for low numbers,the apothecary system over the metric(my age, perhaps, and distrust of pure logic)and the letter W,though most of my colleagues favorM.

I think you can be happy with yellowand, based on my experience,the fact that the straight line is punctuated.Seconds, millimeters--I marvel at their finitude,but this oval, so intricate, so light,might well contain a universe.Is it normal, you ask.Normal's a shell game you seldom win.Take my advice. Enjoy good healthnot as your due but the blessing it islike Spring, laughter,death.

Veneta Masson RN is a nurse and poet living in Washington, DC. She has written three books of essays and poems, drawing on her experiences over twenty years as a family nurse practitioner and director of an inner-city clinic.

“If today you can take a thing like xxxxxxxx and make it a crime to teach it in the public schools, tomorrow you can make it a crime to teach it in the private schools, and next year you can make it a crime to teach it in the church. At the next session you can ban books and the newspapers. Ignorance and fanaticism are ever busy… After a while it is the setting of man against man, creed against creed, until the flying banners and beating drums are marching backwards to the glorious ages of the 16th century when bigots lighted fagots to burn the man who dared to bring any intelligence and enlightenment and culture to the human mind.”

This is the speech of Clarence Darrow in the Scopes trial in Tennessee in 1925. Darrow was speaking against the censorship of evolution in public schools. I wonder if today he would make the same speech against those who want to ban the teaching of Intelligent Design.

I am quoting from a series of articles in New Scientist looking at the difference between Deniers and Sceptics.

Here is the distinction that they make: Scepticism is integral to the scientific process, because most claims turn out to be false. Weeding out the few kernels of wheat from the large pile of chaff requires extensive observation, careful experimentation and cautious inference. Science is scepticism and good scientists are sceptical.

Denial is different. It is the automatic gainsaying of a claim regardless of the evidence for it – sometimes even in the teeth of evidence. Denialism is typically driven by ideology or religious belief, where the commitment to the belief takes precedence over the evidence. Belief comes first, reasons for belief follow, and those reasons are winnowed to ensure that the belief survives intact.

I think that this distinction is too clear cut. Most of us have a belief system that takes a lot of evidence to shake. Many scientists hold on to their beliefs despite convincing evidence that they are wrong. Einstein was ridiculed at first because his ideas contradicted the set Newtonian ideas.

New Scientist identifies seven areas of denial:

Holocaust denial - the assertion that 6 million Jews did not die in concentration camps under the Nazis.Tobacco denial - the assertion that smoking does not cause lung cancer.AIDS denial - denying that HIV causes AIDS.9/11 denial - the assertion that the CIA was responsible for or complicit in the destruction of the twin towers in New York.Vaccine denial - the idea that vaccines either do not work or are harmful (MMR and autism is a version of this)Evolution denial - the idea that species did not arise by gradual change from a primordial soup.Climate change denial - the idea that global warming (1) isn't real (2) isn't caused by humans or (3) doesn't matter.

It seems to me that these denials are by no means of the same order. Holocaust denial involves denying an historical event for which there is much eye-witness testimony. It is certainly true that others besides Jews perished in the concentration camps - homosexuals, Gypsies and the mentally retarded also perished and some Slavs and prisoners of war were also unlawfully murdered by the Nazis. Perhaps 6 million is an inaccurate estimate, but the numbers were very great and even if it were as few as one million (which I think is highly unlikely), the crime would be no less.

9/11 denial is again an historical event which almost everybody watched on television. The idea that it was an Israeli/American plot seems to be so far fetched as to be risible.

Denial that tobacco smoking causes lung cancer flies in the face of epidemiological evidence. Sir Richard Doll, who originally found the link in 1951 was himself a smoker and was looking to air pollution as the cause. He was shocked by his findings and stopped smoking immediately. His data have been confirmed many times since. The evidence against second hand smoke is much less convincing, but I think it is probably correct. Elements of tobacco smoke are certainly carcinogenic in the laboratory, though so is money. Dollar bills sown into the peritoneum of rats led to cancer in one study. Laboratory evidence of carcinogenesis is less reliable that epidemiological evidence.

The original opposition to vaccines came from Jenner's rivals who had a vested interest in the rival technique of variolation. There has always been a strong objection to all forms of vaccination in certain quarters, though goodness knows why, since its benefits are plain to see. All forms of vaccination carry a small risk, but the benefit far outweighs the risk for the population as a whole, though not for the individual who develops encephalitis. Perhaps the idea of the one being risked for the benefit of the many is anathema to people of certain political beliefs. The MMR scam was centered around a particular supposed risk of a specific vaccine. It had the backing of a respected journal (though with a recently appointed showman editor).

Although the theory of evolution has lots of evidence in favour, it depends for its credence the belief that we are not here through supernatural means. A supernatural creation (whether the Mosaic version or another) is not testable by natural means and is therefore beyond science. There are however, a couple of unanswerable criticisms of the neo-Darwinist position. One is how evolution is supposed to have avoided the Second Law of Thermodynamics, since however you look at it, entropy appears to have decreased without any input except raw energy. The second problem is that of irreducible complexity. Supposed gradual improvements occurring by mutation are only improvements in survival if other mutations occur simultaneously – sometimes in a different species. There are many examples of this in nature. It may be that explanations will be forthcoming, but as it stands the attempt to keep God out of it has enormous lacunae.

So called climate deniers seem much more like sceptics to me. The IPCC and its supporters have shot themselves in the foot recently with the East Anglian e-mails and the Himalayan glaciers. It will not do to simply disparage critics by alleging that they are in the pay of big business. It seems to me that the oil companies are backing both sides against the middle. It hardly matters that there is no peer-reviewed literature against the AGW position when there seems to have been a concerted effort by peer reviewers to exclude it.

Most of us are not experts in climate science, but most of us have a good nose for bs. Something about the orthodox position does not smell right.

In science, it is not satisfactory to dismiss one’s critics as heretics. Time after time a new development in science has been held at bay by the old guard.

When I was a young doctor I saw a patient with acute lymphoblastic leukemia who had a Philadelphia chromosome. At that time it was a matter of dogma that the Philadelphia chromosome only occurred in chronic myeloid leukemia, though it would be retained when that disease transformed into acute myeloid leukemia. My case would have involved a paradigm shift, so I took the slides to a Cambridge professor in the hope that he would confirm my findings. He told me that I was in error. This could not be lymphoblastic leukemia because the Philadelphia chromosome only occurred in myeloid tumors.

It was only a couple of years later that it was recognized that the Philadelphia chromosome does indeed occur in acute lymphoblastic leukemia – indeed it is quite common and the main cause of drug resistance. That case made me into a sceptic. I don’t believe experts. The motto of the Royal Society is "nullius in verba" meaning "Take nobody's word for it". So, don't be cowed into believing what the experts tell you. The definition of an expert is - 'ex' = a has been; 'spurt' = a drip under pressure.

Addendum 16th May: Since posting this I have been sent by anonymice links to several Holocaust revisionist sites. I may have hinted that I don't take all the Holocaust propaganda as true, but I don't doubt that there were concentration camps in which millions of Jews, Gypsies, Slavs, homosexuals and mentally retarded individuals died. Some certainly died of typhus and malnutrition - the Belsen film shows this - and I am not getting into the argument on how others died. I decline to publish the links on this site. Thank you for the opportunity, but, no. Start your own blog.

Monday, May 10, 2010

Nodal marginal zone lymphoma resembles what is seen in either the splenic type or MALT lymphoma when it metastasises to lymph nodes, but without the extranodal disease. It is sometimes known as Monocytoid B-cell lymphoma. It comprises less than 2% of B cell lymphomas. Although the median age of presentation is about 60, it can occur in children. In about 20-25% of cases, Hepatitis C can be detected. It affects peripheral lymph nodes and very rarely bone marrow and peripheral blood.

The tumor usually surrounds a reactive follicle and expands into the interfollicular areas. The tumor cells are heterogeneous and are made up of the same sorts of cells seen in MALT lymphomas. The immunophenotype is non-specific and the only common chromosomal abnormalities are trisomies of 3, 7 and 18. The extranodal type translocations are not seen.

The tumor is usually indolent though transformation to a large B-cell lymphoma may occur.

A pediatric form is described. It occurs predominantly in boys (9:1), mainly in head and neck lymph nodes. This tumor is still very indolent and does not require aggressive systemic chemotherapy

Marginal zone lymphomas come in three types. In the past I have written about splenic marginal zone lymphoma (SMZL) also known as splenic lymphoma with villous lymphocytes (SLVL) and I shall say nothing more about that today.

The best known of the marginal zone lymphomas are those occurring in the extranodal mucosa associated lymphoid tissue, the so-called MALT lymphomas. The tumors are morphologically heterogeneous being composed of small centrocytes, monocytoid cells, small round cells and scattered immunoblasts and centroblasts. A proportion of cases show differentiation into plasma cells.

Malt lymphomas comprise 7-8% of B cell lymphomas and about half of gastric lymphomas. Median age of presentation is 61 and there is a slight female preponderance. The association with Helicobacter pylori is well known for gastric lymphomas and there is a similar relationship with Chlamidia psittaci for ocular adenexal Malt lymphoma and with Borrelia burgdorferi (the Lyme disease agent) for cutaneous Malts. There is a rare form of MALT lymphoma which makes immunoglobulin alpha chains and which was once known as alpha heavy chain disease, but is now called immunoproliferative small intestinal disease (IPSID) and which occurs in the middle east and the Cape area of South Africa. This type of MALT is associated with Campylerbacter jejuni. Thyroid and salivary gland MALTs are known to be often preceded by autoimmune processes in the respective glands.

Sites of MALTs are nearly 50% in the gastrointestinal tract, head and neck 14%, lung 14%, eyes 12%, skin 11%, thyroid 4% and breast 4%. Most patients have localised disease with less than 20% showing bone marrow involvement. Involvement of both of paired organs is common. A third of patients have a paraprotein.

The immunophenotype is CD19+, CD20+, CD79a+, CD5-, CD23-, CD10-, CD21+ and CD35+, but there is no specific marker for MALT lymphoma. Chromosomal abnormalities include t(11;18)(q22;q32) in pulmonary and gastric tumors, t(14;18)(q31;q21) in ocular and salivary gland tumors and t(3;14)(p14.1;q32) in ocular, thyroid and skin tumors. Also commonly seen are trisomy 3 and trisomy 18, but these are non-specific.

These tumors are usually indolent and may respond to treatment with appropriate antibiotics. They also tend to be sensitive to radiotherapy.

Baby's Breath flower can boost anti-leukaemia drugs by up to a million times

So read the headline in the Daily Mail.

The article refers to work done in Southampton by David and Bee Flavell with antibodies tagged to Saponin. This couple have been beavering away for more than 20 years ever since they lost their child, Simon, to acute lymphoblastic leukemia.

Here is an abstract of their work from a presentation at the American Association for Cancer Research last month.

Saponins are a highly diverse group of glycosides of plant origin containing either a steroidal or triterpenoid aglycone to which one or more sugar chains are attached. They have been variously described as enhancing the cytotoxic activity of ribosome-inactivating proteins (RIPs) and ligand-directing conjugates constructed with these for eukaryotic cells. Saponins are thought to facilitate the entry of RIPs into the cytosol across the membranes of intracellular vesicular structures. This characteristic of saponins therefore makes them of interest as molecules that could be useful in improving the therapeutic index of immunotoxins (IT) in a clinical setting. In the current study we used a protein synthesis inhibition assay based on leucine incorporation together with cell proliferation studies in culture to demonstrate that saponins from Gypsophila paniculata L. potentiate the cytotoxicity of the anti-CD19 and CD38 saporin-based immunotoxins (BU12-SAPORIN and OKT10-SAPORIN, respectively) by several thousand-fold for the human lymphoma cell line Daudi. Various experiments revealed that the enhancing effect of saponins on immunotoxin activity did not appear to be dependent on extra cellular pH in the assay system we used. Kinetic studies further revealed that saponin at a predetermined optimal concentration of 2 μg/ml reduced the t10 (time taken to reduce protein synthesis to 10% of the level seen in control Daudi cells) for OKT10-SAPORIN at 0.1μg/ml from 50 hours without saponin to 12.5 hours with saponin. In blocking experiments using OKT10-SAPORIN IT at the IC50 concentration in combination with saponin together with a gross excess of native OKT10 antibody we established that the immunospecific cytotoxic activity of OKT10-SAPORIN was fully retained when leucine incorporation was used as the surrogate measure of cytotoxicity but only partially so when thymidine incorporation was used. This observation of a partial uncoupling of protein and DNA synthesis as a measure of cytotoxicity was further supported by cell proliferation experiments in culture which were undertaken in parallel. If saponins are to be of any clinical value as candidate molecules for improving the therapeutic index of immunotoxins it is imperative that the immunospecificity of IT activity is fully retained. Whilst this study clearly demonstrates that saponins from G. paniculata L. do indeed significantly potentiate IT activity it seems that this effect may only be partially immunospecific. Nevertheless, the dramatic improvements that saponins confer on IT activity argue in favor of in vivo experiments in transgenic animal models of human lymphoma combined with additional studies to explore other strategies that might be employed to improve the immunospecific effect achievable.

I have written about these 'immunotoxins' at length in the past and we published a small series back in the 1990s:

AbstractWe report the use of a bispecific F(ab')2 antibody to target the ribosome-inactivating protein saporin to the surface antigen CD22 in the treatment of low-grade, end-stage, B-cell lymphoma. Four patients were treated. Toxic effects were minimal (grade I), with mild fever, weakness, and myalgia for 1-2 days after treatment. One patient showed an antibody response to mouse Fab' and saporin. All patients showed rapid and beneficial responses to treatment with improvements in most disease sites and in peripheral blood cytopenia. The responses were short-lived (less than 28 days) but further study of this targeting system is warranted.We need to distinguish between saporin and saponin. Saporin is a ribosome-inactivating protein similar to ricin, that needs an antibody to hitch a lift on to get into the cell. Saponins are a group of plant compounds which seem to enhance the activity of immunotoxins.

It is important to recognize that these experiments, while promising, are still at the stage of killing cells in a test tube. Many substances kill cells in test tubes, the acid test comes when you put them into patients. We found that the OKT10-saporin conjugate caused transient blindness when given to patients with myeloma.

Saturday, May 08, 2010

One measurement of the quality of healthcare in a country is how safe it is for a woman to get pregnant. It is never entirely safe. There are always going to be some women who die. In the best served countries the number who die is very small, probably fewer than 10 per 100,000 live births. Most countries in Western Europe achieve this. A paper in today's Lancet has looked at records of 181 countries and examinsed whether they have improved since 1980.

Worst of all is the Central African Republic, followed by Malawi and Chad, all with a maternal death rate of greater than 1%. These are some of the poorest countries in the world. HIV is rife and many of these women would have died even if they had not been pregnant. Almost as bad is Afghanistan, which is getting worse, though this might represent better ascertainment now that deaths are more likely to be reported. We should like to see an improvement in healthcare with all those foreign troops there.

Most disappointing is the position of the United States. Again the deterioration here might be due to a different method of counting, but it looks as though it is more than twice as dangerous to have a baby in America than in Sweden.

The UK is about average for Western Europe; the same as Germany. Interestingly France is slightly worse and Italy slightly better, though these differences are at the limit of statistical significance. Cyprus is the big stand-out where things are 5 times as bad - probably because of the high incidence of thalassemia on the island.

In Eastern Europe, both the Czech Republic and Slovakia are down to the levels of Western Europe and Japan, Australia, New Zealand and Canada are down to similar low levels.

The United States is in the next tier with between 10 and 20 maternal deaths per 100,000 pregnancies, along with Portugal, Yemen, Singapore, South Korea, Taiwan, Albania, Hungary, Poland, Serbia, France and the United Arab Emirates.

Things are getting worse in most of sub-Saharan Africa (the influence of AIDS) but they are getting better in much of Asia, North Africa, Latin America and in the former communist states of Eastern Europe.

These comparisons are often not comparing like with like and some countries deliberately mis-state their statistics for reasons of national pride. Again one year's figures often have fairly large confidence intervals, especially in small countries. Nevertheless, there is a stark contrast between rich and poor countries, though it is noticeable that American influence post 1945 has greatly reduced maternal mortality in countries like Japan, Germany, Taiwan, South Korea, Vietnam and the Philippines. However, pariah states like Burma, the Maldives, North Korea and Iran have all improved remarkably.

When the general public opined that following the MP's expenses scandal they ought to be taken out and hanged, the warning should have been beware what you wish for. We now have a hung parliament.

As I write this Conservatives and Liberals are negotiating over whether they can form a government, either in a formal coalition or with a Conservative minority government with tacit Liberal support on most issues.

The big issue is likely to be electoral reform. Because Labour votes are concentrated in big cities with, often, small electorates, the present system favors Labour. The Tories have to be about 10% ahead of Labour in the opinion polls to get an absolute majority. The Tories solution is boundary reform with all constituencies of roughly equal size, and the elimination of small city-center seats.

The Liberals are even worse served by the current system. Despite getting about a quarter of the votes they have less than a tenth of the seats. They want a system of proportional representation, which would give us a parliament which is permanently hung.

With electoral reform, the House of Lords would have to be dealt with. To some extent the Conservatives have put up with a Labor bias in the Commons because of an inbuilt Tory bias in the Lords. Over the past 13 years Labor has tried to redress the balance in the Lords without doing anything to detract from their advantageous position in the Commons.

The current system in the Lords ensures that non-party interests get a say, with churchmen, scientists, doctors, theatre people and businessmen all having a vote. 'The great and the good' are able to stymie unwise legislation.

In the background is the possibility that Labor and the Liberals might cobble together a 'progressive' coalition. However, this would not give them a working majority - they would still need the support of at least some of the Nationalists (Welsh, Scottish and Irish), and this would come with a price (that of sparing those parts of the UK from the cuts that are necessary. Since these parts already enjoy a fiscal advantage over England, this would not go down well with the English. It would bring fresh calls to address the democratic deficit, by which MPs from the smaller nations (including Gordon Brown himself) can have a say on purely English matters, while English MPs have no say on matters that only concern the Celtic nations.

I am troubled about matters of conscience. When I was first qualified in 1967 the British government brought in a law permitting abortion in certain circumstances. As a medical student I had campaigned against it on the scientific grounds that life begins at the fusion of sperm and egg and deliberately eliminating a life is murder whether the life is one day old, 9 months old or 9 years old. Looking back, I would not call my then-self a Christian, though my belief system was heavily influenced by Christian teaching. In my view a case could be made for saving the mother if the pregnancy endangered her life, but even in those circumstances an attempt should be made to save the life of the baby.

At a medical school debate I was opposed by a journalist, Daniel Farson, who was campaigning for abortion. He admitted, when challenged, that the figures on back street abortions were quite bogus, but since his cause was just, what did that matter? "In any case," he argued, "you will be alright. There will be a conscience clause for those who have religious views against abortion, so that they will not be forced to take part."

The same conscience clause was there when they introduced Sunday trading. Shop workers who were already employed would not be forced to work on Sundays if their religion forbade it. However, the strength of the conscience clause was weakened. New workers would not be able to escape Sunday working. If they objected, they should find a job elsewhere.

More recently, new legislation has not included this conscience clause. Catholic adoption agencies were not able to opt out of considering gay couple as adoptors and when civil unions were brought in for homosexuals, Registrars of Births, Deaths and Marriages were expected to conduct ceremonies for gay couples, even if they had religious objections to them. And just last week an employee of Relate, the renamed Marriage Guidance Council, was told by a high court judge that he had no escape from giving advice on sexual techniques to gay couples, even if it was against his conscience.

It is interesting that both the injured parties in the last two cases were black evangelical Christians.

This issue has also raised its head in America. In November 2007, the American College of Obstetrics & Gynecology (ACOG) Ethics Committee issued position statement #385 entitled "The Limits of Conscientious Refusal in Reproductive Medicine."

The first recommendation is: Any conscientious refusal that conflicts with a patient's well-being should be accommodated only if the primary duty to the patient can be fulfilled.

This may sound innocuous, except for the fact that 'patient's well-being' is self-defined. Thus according to ACOG a doctor is required to provide, either by himself or by a proxy, all medical services that are legal, whether or not he has moral objections to a procedure. In Oregon, for example he would be obligated to assist a patient's desire for suicide, if the legal requirements were satisfied. In resource-poor areas where there was no local abortionist, a gynecologist would be obliged to perform the operation if it were withing his competence, according to ACOG. It is notable that there is no other area of medicine where there is a duty to provide for elective procedures; not dermatology; not neurosurgery; not cardiac surgery.

Because of objections to this directive from faith-based organizations ACOG have agreed to look at the issue again. It cannot be stated to strongly that people of faith must contend for what is right. Thomas Paine and Thomas Jefferson, both supported the right of conscience to prevail. We should do no less.

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About Me

Born in Worcester, England 1943; school at Farnborough, Hampshire 1954-62; University 1962-7 and junior doctor posts 1967-74 in Bristol; Consultant Haematologist Bournemouth 1974-2003; Professor of Immunohaematology Southampton 1986 to present. Honorary Consultant Haematologist Kings College Hospital, London, 2004-present. After 5 years of working part time researching, writing, reviewing, editing, speaking, sitting on committees, advising, answering questions and thinking, I now think of myself as fully retired apart from my role as Editor in Chief of the medical journal Leukemia Research. I was awarded the Binet-Rai medal for outstanding research in CLL in 2002 and this has been my most sucessful area of research, but I have also made important contributions in the fields of apheresis, stem cell transplantation, myeloma, myelodysplastic syndrome, antibody therapy, cytokine therapy and DNA vaccines. I was once mascot for Aldershot Town Football. Club. Married to Diane for 44 years. Four children, Karen, Richard, Angela and David.